Leung-Toung Regis, Tam Tim F, Wodzinska Jolanta M, Zhao Yanqing, Lowrie Jayme, Simpson Craig D, Karimian Khashayar, Spino Michael
Department of Medicinal Chemistry, Apotex Research Inc., 400 Ormont Drive, Toronto, ON M9L 1N9, Canada.
J Med Chem. 2005 Apr 7;48(7):2266-9. doi: 10.1021/jm049221w.
A new class of selective FXIIIa inhibitors with a bicyclic [1,2,4]-thiadiazole pharmacophore is described. At 160 muM, compound 8 caused 50% reduction in fibrin gamma-chain cross-linking and suppressed the polymerization of alpha chains in platelet-depleted human plasma clots. Fibrinolysis rates in response to tissue plasminogen activator were directly proportional to the concentration of 8 in plasma at the time of clotting.
描述了一类具有双环[1,2,4]-噻二唑药效基团的新型选择性FXIIIa抑制剂。在160μM时，化合物8使纤维蛋白γ链交联减少50%，并抑制了血小板缺乏的人血浆凝块中α链的聚合。对组织纤溶酶原激活剂的纤溶速率与凝血时血浆中8的浓度成正比。
